Hematopoietic stem and progenitor cells generate all the lineages of blood cells throughout the lifespan of vertebrates. The emergence of hematopoietic stem and progenitor cells is finely tuned by a variety of signaling pathways. Previous studies have revealed the roles of pattern-recognition receptors such as Toll-like receptors and RIG-I-like receptors in hematopoiesis. In this study, we find that Nlrc3, a nucleotide-binding domain leucine-rich repeat containing family gene, is highly expressed in hematopoietic differentiation stages in vivo and vitro and is required in hematopoiesis in zebrafish. Mechanistically, nlrc3 activates the Notch pathway and the downstream gene of Notch hey1. Furthermore, NF-kB signaling acts upstream of nlrc3 to enhance its transcriptional activity. Finally, we find that Nlrc3 signaling is conserved in the regulation of murine embryonic hematopoiesis. Taken together, our findings uncover an indispensable role of Nlrc3 signaling in hematopoietic stem and progenitor cell emergence and provide insights into inflammation-related hematopoietic ontogeny and the in vitro expansion of hematopoietic stem and progenitor cells.

造血干细胞和祖细胞在脊椎动物的整个生命周期中产生所有血细胞谱系。造血干细胞和祖细胞的出现是通过多种信号通路进行微调的。先前的研究揭示了模式识别受体（例如 Toll 样受体和 RIG-I 样受体）在造血中的作用。在本研究中，我们发现Nlrc3是一种富含亮氨酸重复序列的核苷酸结合域家族基因，在体内和体外的造血分化阶段高表达，并且是斑马鱼造血所需的。从机制上讲， nlrc3激活 Notch 通路和 Notch hey1的下游基因。此外，NF-kB 信号传导作用于nlrc3上游，增强其转录活性。最后，我们发现Nlrc3信号在小鼠胚胎造血的调节中是保守的。总而言之，我们的研究结果揭示了Nlrc3信号在造血干细胞和祖细胞出现中不可或缺的作用，并为炎症相关的造血个体发育和造血干细胞和祖细胞的体外扩增提供了见解。